Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA

详细信息    查看全文

• 作者：Madalene A. Earp (1) r> Linda E. Kelemen (2) (3) r> Anthony M. Magliocco (4) r> Kenneth D. Swenerton (5) r> Georgia Chenevix-Trench (6) r> Yi Lu (6) r> Alexander Hein (8) r> Arif B. Ekici (9) r> Matthias W. Beckmann (8) r> Peter A. Fasching (10) (8) r> Diether Lambrechts (11) (12) r> Evelyn Despierre (13) r> Ignace Vergote (13) r> Sandrina Lambrechts (13) r> Jennifer A. Doherty (14) (15) r> Mary Anne Rossing (15) (16) r> Jenny Chang-Claude (17) r> Anja Rudolph (17) r> Grace Friel (18) r> Kirsten B. Moysich (18) r> Kunle Odunsi (18) r> Lara Sucheston-Campbell (18) r> Galina Lurie (19) r> Marc T. Goodman (20) r> Michael E. Carney (19) r> Pamela J. Thompson (20) r> Ingo B. Runnebaum (21) r> Matthias Dürst (21) r> Peter Hillemanns (22) r> Thilo D?rk (23) r> Natalia Antonenkova (24) r> Natalia Bogdanova (23) r> Arto Leminen (25) r> Heli Nevanlinna (25) r> Liisa M. Pelttari (25) r> Ralf Butzow (25) (26) r> Clareann H. Bunker (27) r> Francesmary Modugno (27) (28) (29) r> Robert P. Edwards (28) (29) r> Roberta B. Ness (30) r> Andreas du Bois (31) (32) r> Florian Heitz (31) (32) r> Ira Schwaab (33) r> Philipp Harter (31) (32) r> Beth Y. Karlan (34) r> Christine Walsh (34) r> Jenny Lester (34) r> Allan Jensen (35) r> Susanne K. Kj?r (35) (36) r> Claus K. H?gdall (36) r> Estrid H?gdall (35) (37) r> Lene Lundvall (36) r> Thomas A. Sellers (38) r> Brooke L. Fridley (39) r> Ellen L. Goode (40) r> Julie M. Cunningham (41) r> Robert A. Vierkant (42) r> Graham G. Giles (43) (44) r> Laura Baglietto (43) (44) r> Gianluca Severi (43) (44) r> Melissa C. Southey (45) r> Dong Liang (46) r> Xifeng Wu (47) r> Karen Lu (48) r> Michelle A. T. Hildebrandt (47) r> Douglas A. Levine (49) r> Maria Bisogna (49) r> Joellen M. Schildkraut (50) (51) r> Edwin S. Iversen (51) (52) r> Rachel Palmieri Weber (50) r> Andrew Berchuck (53) r> Daniel W. Cramer (54) (55) r> Kathryn L. Terry (54) (55) r> Elizabeth M. Poole (55) (56) r> Shelley S. Tworoger (55) (56) r> Elisa V. Bandera (57) r> Urmila Chandran (57) r> Irene Orlow (58) r> Sara H. Olson (58) r> Elisabeth Wik (59) (60) r> Helga B. Salvesen (60) (61) r> Line Bjorge (60) (61) r> Mari K. Halle (60) (61) r> Anne M. van Altena (62) r> Katja K. H. Aben (63) (64) r> Lambertus A. Kiemeney (63) (65) r> Leon F. A. G. Massuger (62) r> Tanja Pejovic (66) (67) r> Yukie T. Bean (66) (67) r> Cezary Cybulski (68) r> Jacek Gronwald (68) r> Jan Lubinski (68) r> Nicolas Wentzensen (69) r> Louise A. Brinton (69) r> Jolanta Lissowska (70) r> Montserrat Garcia-Closas (71) (72) r> Ed Dicks (73) r> Joe Dennis (74) r> Douglas F. Easton (74) r> Honglin Song (73) r> Jonathan P. Tyrer (73) r> Paul D. P. Pharoah (73) (74) r> Diana Eccles (75) r> Ian G. Campbell (45) (7) (76) r> Alice S. Whittemore (77) r> Valerie McGuire (77) r> Weiva Sieh (77) r> Joseph H. Rothstein (77) r> James M. Flanagan (78) r> James Paul (79) r> Robert Brown (78) r> Catherine M. Phelan (38) r> Harvey A. Risch (80) r> John R. McLaughlin (81) r> Steven A. Narod (82) r> Argyrios Ziogas (83) r> Hoda Anton-Culver (83) r> Aleksandra Gentry-Maharaj (84) r> Usha Menon (84) r> Simon A. Gayther (85) r> Susan J. Ramus (85) r> Anna H. Wu (85) r> Celeste L. Pearce (85) r> Malcolm C. Pike (58) (85) r> Agnieszka Dansonka-Mieszkowska (86) r> Iwona K. Rzepecka (86) r> Lukasz M. Szafron (86) r> Jolanta Kupryjanczyk (86) r> Linda S. Cook (2) (87) (88) r> Nhu D. Le (89) r> Angela Brooks-Wilson (1) (90) r>
• 刊名：Human Genetics
• 出版年：2014
• 出版时间：May 2014
• 年：2014
• 卷：133
• 期：5
• 页码：481-497
• 全文大小：1,557 KB
• 参考文献：1. Albarracin CT, Silva EG, Malpica A, Luthra R, Liu J (2004) The role of hMSH3 and hMSH6 in ovarian endometrioid carcinoma and relationship with microsatellite instability phenotype. Oncol Rep 12:1217-219 r> 2. Bojesen SE, Pooley KA, Johnatty SE, Beesley J, Michailidou K, Tyrer JP, Edwards SL, Pickett HA, Shen HC, Smart CE, Hillman KM, Mai PL, Lawrenson K, Stutz MD, Lu Y, Karevan R, Woods N, Johnston RL, French JD, Chen X, Weischer M, Nielsen SF, Maranian MJ, Ghoussaini M, Ahmed S, Baynes C, Bolla MK, Wang Q, Dennis J, McGuffog L, Barrowdale D, Lee A, Healey S, Lush M, Tessier DC, Vincent D, Bacot F, Vergote I, Lambrechts S, Despierre E, Risch HA, Gonzalez-Neira A, Rossing MA, Pita G, Doherty JA, Alvarez N, Larson MC, Fridley BL, Schoof N, Chang-Claude J, Cicek MS, Peto J, Kalli KR, Broeks A, Armasu SM, Schmidt MK, Braaf LM, Winterhoff B, Nevanlinna H, Konecny GE, Lambrechts D, Rogmann L, Guenel P, Teoman A, Milne RL, Garcia JJ, Cox A, Shridhar V, Burwinkel B, Marme F, Hein R, Sawyer EJ, Haiman CA, Wang-Gohrke S, Andrulis IL, Moysich KB, Hopper JL, Odunsi K, Lindblom A, Giles GG, Brenner H, Simard J, Lurie G, Fasching PA, Carney ME, Radice P, Wilkens LR, Swerdlow A, Goodman MT, Brauch H, Garcia-Closas M, Hillemanns P, Winqvist R, Durst M, Devilee P, Runnebaum I, Jakubowska A, Lubinski J, Mannermaa A, Butzow R et al (2013) Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet 45:371-84. doi:rl-ref">10.1038/ng.2566 (384e1-) r> 3. Bolton KL, Tyrer J, Song H, Ramus SJ, Notaridou M, Jones C, Sher T, Gentry-Maharaj A, Wozniak E, Tsai YY, Weidhaas J, Paik D, Van Den Berg DJ, Stram DO, Pearce CL, Wu AH, Brewster W, Anton-Culver H, Ziogas A, Narod SA, Levine DA, Kaye SB, Brown R, Paul J, Flanagan J, Sieh W, McGuire V, Whittemore AS, Campbell I, Gore ME, Lissowska J, Yang HP, Medrek K, Gronwald J, Lubinski J, Jakubowska A, Le ND, Cook LS, Kelemen LE, Brook-Wilson A, Massuger LF, Kiemeney LA, Aben KK, van Altena AM, Houlston R, Tomlinson I, Palmieri RT, Moorman PG, Schildkraut J, Iversen ES, Phelan C, Vierkant RA, Cunningham JM, Goode EL, Fridley BL, Kruger-Kjaer S, Blaeker J, Hogdall E, Hogdall C, Gross J, Karlan BY, Ness RB, Edwards RP, Odunsi K, Moyisch KB, Baker JA, Modugno F, Heikkinenen T, Butzow R, Nevanlinna H, Leminen A, Bogdanova N, Antonenkova N, Doerk T, Hillemanns P, Durst M, Runnebaum I, Thompson PJ, Carney ME, Goodman MT, Lurie G, Wang-Gohrke S, Hein R, Chang-Claude J, Rossing MA, Cushing-Haugen KL, Doherty J, Chen C, Rafnar T, Besenbacher S, Sulem P, Stefansson K, Birrer MJ, Terry KL, Hernandez D, Cramer DW, Vergote I, Amant F, Lambrechts D, Despierre E et al (2010) Common variants at 19p13 are associated with susceptibility to ovarian cancer. Nat Genet 42:880-84. doi:rl-ref">10.1038/ng.666 r> 4. Brown KM, Macgregor S, Montgomery GW, Craig DW, Zhao ZZ, Iyadurai K, Henders AK, Homer N, Campbell MJ, Stark M, Thomas S, Schmid H, Holland EA, Gillanders EM, Duffy DL, Maskiell JA, Jetann J, Ferguson M, Stephan DA, Cust AE, Whiteman D, Green A, Olsson H, Puig S, Ghiorzo P, Hansson J, Demenais F, Goldstein AM, Gruis NA, Elder DE, Bishop JN, Kefford RF, Giles GG, Armstrong BK, Aitken JF, Hopper JL, Martin NG, Trent JM, Mann GJ, Hayward NK (2008) Common sequence variants on 20q11.22 confer melanoma susceptibility. Nat Genet 40:838-40. doi:rl-ref">10.1038/ng.163 r> 5. Cai KQ, Albarracin C, Rosen D, Zhong R, Zheng W, Luthra R, Broaddus R, Liu J (2004) Microsatellite instability and alteration of the expression of hMLH1 and hMSH2 in ovarian clear cell carcinoma. Hum Pathol 35:552-59 (pii:S0046817704000450) r> 6. Catasus L, Bussaglia E, Rodrguez I, Gallardo A, Pons C, Irving JA, Prat J (2004) Molecular genetic alterations in endometrioid carcinomas of the ovary: similar frequency of beta-catenin abnormalities but lower rate of microsatellite instability and PTEN alterations than in uterine endometrioid carcinomas. Hum Pathol 35:1360-368. doi:rl-ref">10.1016/j.humpath.2004.07.019 r> 7. Earp MA, Rahmani M, Chew K, Brooks-Wilson A (2011) Estimates of array and pool-construction variance for planning efficient DNA-pooling genome wide association studies. BMC Med Genomics 4:81. doi:rl-ref">10.1186/1755-8794-4-81 r> 8. Faber MT, Kjaer SK, Dehlendorff C, Chang-Claude J, Andersen KK, Hogdall E, Webb PM, Jordan SJ, Rossing MA, Doherty JA, Lurie G, Thompson PJ, Carney ME, Goodman MT, Ness RB, Modugno F, Edwards RP, Bunker CH, Goode EL, Fridley BL, Vierkant RA, Larson MC, Schildkraut J, Cramer DW, Terry KL, Vitonis AF, Bandera EV, Olson SH, King M, Chandran U, Kiemeney LA, Massuger LF, van Altena AM, Vermeulen SH, Brinton L, Wentzensen N, Lissowska J, Yang HP, Moysich KB, Odunsi K, Kasza K, Odunsi-Akanji O, Song H, Pharaoh P, Shah M, Whittemore AS, McGuire V, Sieh W, Sutphen R, Menon U, Gayther SA, Ramus SJ, Gentry-Maharaj A, Pearce CL, Wu AH, Pike MC, Risch HA, Jensen A (2013) Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case–control studies. Cancer Causes Control 24:989-004. doi:rl-ref">10.1007/s10552-013-0174-4 r> 9. Gayther SA, Pharoah PD (2010) The inherited genetics of ovarian and endometrial cancer. Curr Opin Genet Dev 20:231-38. doi:rl-ref">10.1016/j.gde.2010.03.001 r> 10. Gilks CB (2010) Molecular abnormalities in ovarian cancer subtypes other than high-grade serous carcinoma. J Oncol 2010:740968. doi:rl-ref">10.1155/2010/740968 r> 11. Gilks CB, Prat J (2009) Ovarian carcinoma pathology and genetics: recent advances. Hum Pathol 40:1213-223. doi:rl-ref">10.1016/j.humpath.2009.04.017 r> 12. Gilks CB, Ionescu DN, Kalloger SE, Kobel M, Irving J, Clarke B, Santos J, Le N, Moravan V, Swenerton K, Cheryl Brown Ovarian Cancer Outcomes Unit of the British Columbia Cancer A (2008) Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma. Hum Pathol 39:1239-251. doi:rl-ref">10.1016/j.humpath.2008.01.003 r> 13. Gomez-Raposo C, Mendiola M, Barriuso J, Hardisson D, Redondo A (2010) Molecular characterization of ovarian cancer by gene-expression profiling. Gynecol Oncol 118:88-2. doi:rl-ref">10.1016/j.ygyno.2010.03.012 r> 14. Goode EL, Chenevix-Trench G, Song H, Ramus SJ, Notaridou M, Lawrenson K, Widschwendter M, Vierkant RA, Larson MC, Kjaer SK, Birrer MJ, Berchuck A, Schildkraut J, Tomlinson I, Kiemeney LA, Cook LS, Gronwald J, Garcia-Closas M, Gore ME, Campbell I, Whittemore AS, Sutphen R, Phelan C, Anton-Culver H, Pearce CL, Lambrechts D, Rossing MA, Chang-Claude J, Moysich KB, Goodman MT, Dork T, Nevanlinna H, Ness RB, Rafnar T, Hogdall C, Hogdall E, Fridley BL, Cunningham JM, Sieh W, McGuire V, Godwin AK, Cramer DW, Hernandez D, Levine D, Lu K, Iversen ES, Palmieri RT, Houlston R, van Altena AM, Aben KK, Massuger LF, Brooks-Wilson A, Kelemen LE, Le ND, Jakubowska A, Lubinski J, Medrek K, Stafford A, Easton DF, Tyrer J, Bolton KL, Harrington P, Eccles D, Chen A, Molina AN, Davila BN, Arango H, Tsai YY, Chen Z, Risch HA, McLaughlin J, Narod SA, Ziogas A, Brewster W, Gentry-Maharaj A, Menon U, Wu AH, Stram DO, Pike MC, Wellcome Trust Case-Control C, Beesley J, Webb PM, Australian Cancer S, Australian Ovarian Cancer Study G, Ovarian Cancer Association C, Chen X, Ekici AB, Thiel FC, Beckmann MW, Yang H, Wentzensen N, Lissowska J, Fasching PA, Despierre E, Amant F, Vergote I, Doherty J, Hein R, Wang-Gohrke S, Lurie G et al (2010) A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nat Genet 42:874-79. doi:rl-ref">10.1038/ng.668 r> 15. Hacker C, Valchanova R, Adams S, Munz B (2010) ZFP36L1 is regulated by growth factors and cytokines in keratinocytes and influences their VEGF production. Growth Factors 28:178-90. doi:rl-ref">10.3109/08977190903578660 r> 16. Han G, Gilks CB, Leung S, Ewanowich CA, Irving JA, Longacre TA, Soslow RA (2008) Mixed ovarian epithelial carcinomas with clear cell and serous components are variants of high-grade serous carcinoma: an interobserver correlative and immunohistochemical study of 32 cases. Am J Surg Pathol 32:955-64. doi:rl-ref">10.1097/PAS.0b013e318164edf7 r> 17. Ho AS, Kannan K, Roy DM, Morris LG, Ganly I, Katabi N, Ramaswami D, Walsh LA, Eng S, Huse JT, Zhang J, Dolgalev I, Huberman K, Heguy A, Viale A, Drobnjak M, Leversha MA, Rice CE, Singh B, Iyer NG, Leemans CR, Bloemena E, Ferris RL, Seethala RR, Gross BE, Liang Y, Sinha R, Peng L, Raphael BJ, Turcan S, Gong Y, Schultz N, Kim S, Chiosea S, Shah JP, Sander C, Lee W, Chan TA (2013) The mutational landscape of adenoid cystic carcinoma. Nat Genet. doi:rl-ref">10.1038/ng.2643 r> 18. Homer N, Tembe WD, Szelinger S, Redman M, Stephan DA, Pearson JV, Nelson SF, Craig D (2008) Multimarker analysis and imputation of multiple platform pooling-based genome-wide association studies. Bioinformatics (Oxford, England) 24:1896-902. doi:rl-ref">10.1093/bioinformatics/btn333 r> 19. Hsu PP, Kang SA, Rameseder J, Zhang Y, Ottina KA, Lim D, Peterson TR, Choi Y, Gray NS, Yaffe MB, Marto JA, Sabatini DM (2011) The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332:1317-322. doi:rl-ref">10.1126/science.1199498332/6035/1317 r> 20. Jones S, Wang TL, Shih Ie M, Mao TL, Nakayama K, Roden R, Glas R, Slamon D, Diaz LA Jr, Vogelstein B, Kinzler KW, Velculescu VE, Papadopoulos N (2010) Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science 330:228-31. doi:rl-ref">10.1126/science.1196333 r> 21. Kalloger SE, Kobel M, Leung S, Mehl E, Gao D, Marcon KM, Chow C, Clarke BA, Huntsman DG, Gilks CB (2010) Calculator for ovarian carcinoma subtype prediction. Mod Pathol: Off J US Can Acad Pathol Inc. doi:rl-ref">10.1038/modpathol.2010.215 r> 22. Kelemen LE, Kobel M (2011) Mucinous carcinomas of the ovary and colorectum: different organ, same dilemma. Lancet Oncol 12:1071-080. doi:rl-ref">10.1016/S1470-2045(11)70058-4 r> 23. Kobel M, Kalloger SE, Carrick J, Huntsman D, Asad H, Oliva E, Ewanowich CA, Soslow RA, Gilks CB (2009) A limited panel of immunomarkers can reliably distinguish between clear cell and high-grade serous carcinoma of the ovary. Am J Surg Pathol 33:14-1. doi:rl-ref">10.1097/PAS.0b013e3181788546 r> 24. Kobel M, Kalloger SE, Baker PM, Ewanowich CA, Arseneau J, Zherebitskiy V, Abdulkarim S, Leung S, Duggan MA, Fontaine D, Parker R, Huntsman DG, Gilks CB (2010) Diagnosis of ovarian carcinoma cell type is highly reproducible: a transcanadian study. Am J Surg Pathol 34:984-93. doi:rl-ref">10.1097/PAS.0b013e3181e1a3bb r> 25. Kuo KT, Mao TL, Jones S, Veras E, Ayhan A, Wang TL, Glas R, Slamon D, Velculescu VE, Kuman RJ, Shih Ie M (2009) Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma. Am J Pathol 174:1597-601. doi:rl-ref">10.2353/ajpath.2009.081000 r> 26. Kurman RJ, Ronnett BM (2010) Ovarian intestinal-type mucinous borderline tumors: a nomenclature change is long overdue. Int J Gynecol Pathol 29:552-53. doi:rl-ref">10.1097/PGP.0b013e3181eb2fb5 (author reply 553-) r> 27. Kurman RJ, Shih I (2010) The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol 34:433-43. doi:rl-ref">10.1097/PAS.0b013e3181cf3d79 r> 28. Lynch HT, Schuelke GS, Kimberling WJ, Albano WA, Lynch JF, Biscone KA, Lipkin ML, Deschner EE, Mikol YB, Sandberg AA et al (1985) Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). II. Biomarker studies. Cancer 56:939-51 r> 29. Lynch HT, Conway T, Lynch J (1991) Hereditary ovarian cancer. Pedigree studies, Part II. Cancer Genet Cytogenet 53:161-83 (pii:0165-4608(91)90094-B) r> 30. Matsuno RK, Sherman ME, Visvanathan K, Goodman MT, Hernandez BY, Lynch CF, Ioffe OB, Horio D, Platz C, Altekruse SF, Pfeiffer RM, Anderson WF (2013) Agreement for tumor grade of ovarian carcinoma: analysis of archival tissues from the surveillance, epidemiology, and end results residual tissue repository. Cancer Causes Control 24:749-57. doi:rl-ref">10.1007/s10552-013-0157-5 r> 31. Mulero JJ, Boyle BJ, Bradley S, Bright JM, Nelken ST, Ho TT, Mize NK, Childs JD, Ballinger DG, Ford JE, Rupp F (2002) Three new human members of the lipid transfer/lipopolysaccharide binding protein family (LT/LBP). Immunogenetics 54:293-00. doi:rl-ref">10.1007/s00251-002-0467-3 r> 32. Obata K, Morland SJ, Watson RH, Hitchcock A, Chenevix-Trench G, Thomas EJ, Campbell IG (1998) Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors. Cancer Res 58:2095-097 r> 33. Pearce CL, Templeman C, Rossing MA, Lee A, Near AM, Webb PM, Nagle CM, Doherty JA, Cushing-Haugen KL, Wicklund KG, Chang-Claude J, Hein R, Lurie G, Wilkens LR, Carney ME, Goodman MT, Moysich K, Kjaer SK, Hogdall E, Jensen A, Goode EL, Fridley BL, Larson MC, Schildkraut JM, Palmieri RT, Cramer DW, Terry KL, Vitonis AF, Titus LJ, Ziogas A, Brewster W, Anton-Culver H, Gentry-Maharaj A, Ramus SJ, Anderson AR, Brueggmann D, Fasching PA, Gayther SA, Huntsman DG, Menon U, Ness RB, Pike MC, Risch H, Wu AH, Berchuck A, on behalf of the Ovarian Cancer Association C (2012) Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol. doi:rl-ref">10.1016/s1470-2045(11)70404-1 r> 34. Pearson JV, Huentelman MJ, Halperin RF, Tembe WD, Melquist S, Homer N, Brun M, Szelinger S, Coon KD, Zismann VL, Webster JA, Beach T, Sando SB, Aasly JO, Heun R, Jessen F, Kolsch H, Tsolaki M, Daniilidou M, Reiman EM, Papassotiropoulos A, Hutton ML, Stephan DA, Craig DW (2007) Identification of the genetic basis for complex disorders by use of pooling-based genomewide single-nucleotide-polymorphism association studies. Am J Hum Genet 80:126-39. doi:rl-ref">10.1086/510686 r> 35. Permuth-Wey J, Lawrenson K, Shen HC, Velkova A, Tyrer JP, Chen Z, Lin HY, Chen YA, Tsai YY, Qu X, Ramus SJ, Karevan R, Lee J, Lee N, Larson MC, Aben KK, Anton-Culver H, Antonenkova N, Antoniou AC, Armasu SM, Bacot F, Baglietto L, Bandera EV, Barnholtz-Sloan J, Beckmann MW, Birrer MJ, Bloom G, Bogdanova N, Brinton LA, Brooks-Wilson A, Brown R, Butzow R, Cai Q, Campbell I, Chang-Claude J, Chanock S, Chenevix-Trench G, Cheng JQ, Cicek MS, Coetzee GA, Cook LS, Couch FJ, Cramer DW, Cunningham JM, Dansonka-Mieszkowska A, Despierre E, Doherty JA, Dork T, du Bois A, Durst M, Easton DF, Eccles D, Edwards R, Ekici AB, Fasching PA, Fenstermacher DA, Flanagan JM, Garcia-Closas M, Gentry-Maharaj A, Giles GG, Glasspool RM, Gonzalez-Bosquet J, Goodman MT, Gore M, Gorski B, Gronwald J, Hall P, Halle MK, Harter P, Heitz F, Hillemanns P, Hoatlin M, Hogdall CK, Hogdall E, Hosono S, Jakubowska A, Jensen A, Jim H, Kalli KR, Karlan BY, Kaye SB, Kelemen LE, Kiemeney LA, Kikkawa F, Konecny GE, Krakstad C, Kjaer SK, Kupryjanczyk J, Lambrechts D, Lambrechts S, Lancaster JM, Le ND, Leminen A, Levine DA, Liang D, Lim BK, Lin J, Lissowska J, Lu KH, Lubinski J, et al (2013) Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31. Nat Commun 4:1627. doi:rl-ref">10.1038/ncomms2613ncomms2613 r> 36. Pharoah PD, Tsai YY, Ramus SJ, Phelan CM, Goode EL, Lawrenson K, Buckley M, Fridley BL, Tyrer JP, Shen H, Weber R, Karevan R, Larson MC, Song H, Tessier DC, Bacot F, Vincent D, Cunningham JM, Dennis J, Dicks E, Aben KK, Anton-Culver H, Antonenkova N, Armasu SM, Baglietto L, Bandera EV, Beckmann MW, Birrer MJ, Bloom G, Bogdanova N, Brenton JD, Brinton LA, Brooks-Wilson A, Brown R, Butzow R, Campbell I, Carney ME, Carvalho RS, Chang-Claude J, Chen YA, Chen Z, Chow WH, Cicek MS, Coetzee G, Cook LS, Cramer DW, Cybulski C, Dansonka-Mieszkowska A, Despierre E, Doherty JA, Dork T, du Bois A, Durst M, Eccles D, Edwards R, Ekici AB, Fasching PA, Fenstermacher D, Flanagan J, Gao YT, Garcia-Closas M, Gentry-Maharaj A, Giles G, Gjyshi A, Gore M, Gronwald J, Guo Q, Halle MK, Harter P, Hein A, Heitz F, Hillemanns P, Hoatlin M, Hogdall E, Hogdall CK, Hosono S, Jakubowska A, Jensen A, Kalli KR, Karlan BY, Kelemen LE, Kiemeney LA, Kjaer SK, Konecny GE, Krakstad C, Kupryjanczyk J, Lambrechts D, Lambrechts S, Le ND, Lee N, Lee J, Leminen A, Lim BK, Lissowska J, Lubinski J, Lundvall L, Lurie G, Massuger LF, Matsuo K, McGuire V et al (2013) GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer. Nat Genet 45:362-70. doi:rl-ref">10.1038/ng.2564ng.2564 r> 37. Piek JM, van Diest PJ, Zweemer RP, Jansen JW, Poort-Keesom RJ, Menko FH, Gille JJ, Jongsma AP, Pals G, Kenemans P, Verheijen RH (2001) Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer. J Pathol 195:451-56. doi:rl-ref">10.1002/path.1000 r> 38. Planel S, Salomon A, Jalinot P, Feige JJ, Cherradi N (2010) A novel concept in antiangiogenic and antitumoral therapy: multitarget destabilization of short-lived mRNAs by the zinc finger protein ZFP36L1. Oncogene 29:5989-003. doi:rl-ref">10.1038/onc.2010.341 r> 39. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559-75. doi:rl-ref">10.1086/519795 r> 40. Sambrook JRD (2000) Molecular cloning: a laboratory manual (3rd edition). Cold Spring Harbor Laboratory Press, USA r> 41. Schrauwen I, Ealy M, Huentelman MJ, Thys M, Homer N, Vanderstraeten K, Fransen E, Corneveaux JJ, Craig DW, Claustres M, Cremers CW, Dhooge I, Van de Heyning P, Vincent R, Offeciers E, Smith RJ, Van Camp G (2009) A genome-wide analysis identifies genetic variants in the RELN gene associated with otosclerosis. Am J Hum Genet 84:328-38. doi:rl-ref">10.1016/j.ajhg.2009.01.023 r> 42. Shen H, Fridley BL, Song H, Lawrenson K, Cunningham JM, Ramus SJ, Cicek MS, Tyrer J, Stram D, Larson MC, Kobel M, Ziogas A, Zheng W, Yang HP, Wu AH, Wozniak EL, Woo YL, Winterhoff B, Wik E, Whittemore AS, Wentzensen N, Weber RP, Vitonis AF, Vincent D, Vierkant RA, Vergote I, Van Den Berg D, Van Altena AM, Tworoger SS, Thompson PJ, Tessier DC, Terry KL, Teo SH, Templeman C, Stram DO, Southey MC, Sieh W, Siddiqui N, Shvetsov YB, Shu XO, Shridhar V, Wang-Gohrke S, Severi G, Schwaab I, Salvesen HB, Rzepecka IK, Runnebaum IB, Rossing MA, Rodriguez–Rodriguez L, Risch HA, Renner SP, Poole EM, Pike MC, Phelan CM, Pelttari LM, Pejovic T, Paul J, Orlow I, Omar SZ, Olson SH, Odunsi K, Nickels S, Nevanlinna H, Ness RB, Narod SA, Nakanishi T, Moysich KB, Monteiro AN, Moes-Sosnowska J, Modugno F, Menon U, McLaughlin JR, McGuire V, Matsuo K, Adenan NA, Massuger LF, Lurie G, Lundvall L, Lubinski J, Lissowska J, Levine DA, Leminen A, Lee AW, Le ND, Lambrechts S, Lambrechts D, Kupryjanczyk J, Krakstad C, Konecny GE, Kjaer SK, Kiemeney LA, Kelemen LE, Keeney GL, Karlan BY, Karevan R, Kalli KR, Kajiyama H, Ji BT, Jensen A, Jakubowska A et al (2013) Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer. Nat Commun 4:1628. doi:rl-ref">10.1038/ncomms2629 r> 43. Shulman LP (2010) Hereditary breast and ovarian cancer (HBOC): clinical features and counseling for BRCA1 and BRCA2, Lynch syndrome, Cowden syndrome, and Li-Fraumeni syndrome. Obstet Gynecol Clin N Am 37:109-33. doi:rl-ref">10.1016/j.ogc.2010.03.003 (Table of contents) r> 44. Skibola CF, Bracci PM, Halperin E, Conde L, Craig DW, Agana L, Iyadurai K, Becker N, Brooks-Wilson A, Curry JD, Spinelli JJ, Holly EA, Riby J, Zhang L, Nieters A, Smith MT, Brown KM (2009) Genetic variants at 6p21.33 are associated with susceptibility to follicular lymphoma. Nat Genet 41:873-75. doi:rl-ref">10.1038/ng.419 r> 45. Song H, Ramus SJ, Tyrer J, Bolton KL, Gentry-Maharaj A, Wozniak E, Anton-Culver H, Chang-Claude J, Cramer DW, DiCioccio R, Dork T, Goode EL, Goodman MT, Schildkraut JM, Sellers T, Baglietto L, Beckmann MW, Beesley J, Blaakaer J, Carney ME, Chanock S, Chen Z, Cunningham JM, Dicks E, Doherty JA, Durst M, Ekici AB, Fenstermacher D, Fridley BL, Giles G, Gore ME, De Vivo I, Hillemanns P, Hogdall C, Hogdall E, Iversen ES, Jacobs IJ, Jakubowska A, Li D, Lissowska J, Lubinski J, Lurie G, McGuire V, McLaughlin J, Medrek K, Moorman PG, Moysich K, Narod S, Phelan C, Pye C, Risch H, Runnebaum IB, Severi G, Southey M, Stram DO, Thiel FC, Terry KL, Tsai YY, Tworoger SS, Van Den Berg DJ, Vierkant RA, Wang-Gohrke S, Webb PM, Wilkens LR, Wu AH, Yang H, Brewster W, Ziogas A, Australian Cancer S, Australian Ovarian Cancer Study G, Ovarian Cancer Association C, Houlston R, Tomlinson I, Whittemore AS, Rossing MA, Ponder BA, Pearce CL, Ness RB, Menon U, Kjaer SK, Gronwald J, Garcia-Closas M, Fasching PA, Easton DF, Chenevix-Trench G, Berchuck A, Pharoah PD, Gayther SA (2009) A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2. Nat Genet 41:996-000. doi:rl-ref">10.1038/ng.424 r> 46. Stewart CJ, Leung Y, Walsh MD, Walters RJ, Young JP, Buchanan DD (2012) KRAS mutations in ovarian low-grade endometrioid adenocarcinoma: association with concurrent endometriosis. Hum Pathol 43:1177-183. doi:rl-ref">10.1016/j.humpath.2011.10.009 r> 47. Tavassoulu FA, Devilee P (2003) World Health Organization classification of tumors. Pathology and genetics of tumors of the breast and female genital organs. IARC Breast r> 48. Tothill RW, Tinker AV, George J, Brown R, Fox SB, Lade S, Johnson DS, Trivett MK, Etemadmoghadam D, Locandro B, Traficante N, Fereday S, Hung JA, Chiew YE, Haviv I, Gertig D, DeFazio A, Bowtell DD (2008) Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clin Cancer Res 14:5198-208. doi:rl-ref">10.1158/1078-0432.CCR-08-019614/16/5198 r> 49. Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, Friedlander M, Gabra H, Kaye SB, Lord CJ, Lengyel E, Levine DA, McNeish IA, Menon U, Mills GB, Nephew KP, Oza AM, Sood AK, Stronach EA, Walczak H, Bowtell DD, Balkwill FR (2011) Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer 11:719-25. doi:rl-ref">10.1038/nrc3144 r> 50. Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, Senz J, McConechy MK, Anglesio MS, Kalloger SE, Yang W, Heravi-Moussavi A, Giuliany R, Chow C, Fee J, Zayed A, Prentice L, Melnyk N, Turashvili G, Delaney AD, Madore J, Yip S, McPherson AW, Ha G, Bell L, Fereday S, Tam A, Galletta L, Tonin PN, Provencher D, Miller D, Jones SJ, Moore RA, Morin GB, Oloumi A, Boyd N, Aparicio SA, Shih I, Mes-Masson AM, Bowtell DD, Hirst M, Gilks B, Marra MA, Huntsman DG (2010) ARID1A mutations in endometriosis-associated ovarian carcinomas. New Eng J Med 363:1532-543. doi:rl-ref">10.1056/NEJMoa1008433 r> 51. Xu Z, Taylor JA (2009) SNPinfo: integrating GWAS and candidate gene information into functional SNP selection for genetic association studies. Nucleic Acids Res 37:W600–W605. doi:rl-ref">10.1093/nar/gkp290 r> 52. Yu Y, Yoon SO, Poulogiannis G, Yang Q, Ma XM, Villen J, Kubica N, Hoffman GR, Cantley LC, Gygi SP, Blenis J (2011) Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 332:1322-326. doi:rl-ref">10.1126/science.1199484332/6035/1322 r>
• 作者单位：Madalene A. Earp (1) r> Linda E. Kelemen (2) (3) r> Anthony M. Magliocco (4) r> Kenneth D. Swenerton (5) r> Georgia Chenevix-Trench (6) r> Yi Lu (6) r> Alexander Hein (8) r> Arif B. Ekici (9) r> Matthias W. Beckmann (8) r> Peter A. Fasching (10) (8) r> Diether Lambrechts (11) (12) r> Evelyn Despierre (13) r> Ignace Vergote (13) r> Sandrina Lambrechts (13) r> Jennifer A. Doherty (14) (15) r> Mary Anne Rossing (15) (16) r> Jenny Chang-Claude (17) r> Anja Rudolph (17) r> Grace Friel (18) r> Kirsten B. Moysich (18) r> Kunle Odunsi (18) r> Lara Sucheston-Campbell (18) r> Galina Lurie (19) r> Marc T. Goodman (20) r> Michael E. Carney (19) r> Pamela J. Thompson (20) r> Ingo B. Runnebaum (21) r> Matthias Dürst (21) r> Peter Hillemanns (22) r> Thilo D?rk (23) r> Natalia Antonenkova (24) r> Natalia Bogdanova (23) r> Arto Leminen (25) r> Heli Nevanlinna (25) r> Liisa M. Pelttari (25) r> Ralf Butzow (25) (26) r> Clareann H. Bunker (27) r> Francesmary Modugno (27) (28) (29) r> Robert P. Edwards (28) (29) r> Roberta B. Ness (30) r> Andreas du Bois (31) (32) r> Florian Heitz (31) (32) r> Ira Schwaab (33) r> Philipp Harter (31) (32) r> Beth Y. Karlan (34) r> Christine Walsh (34) r> Jenny Lester (34) r> Allan Jensen (35) r> Susanne K. Kj?r (35) (36) r> Claus K. H?gdall (36) r> Estrid H?gdall (35) (37) r> Lene Lundvall (36) r> Thomas A. Sellers (38) r> Brooke L. Fridley (39) r> Ellen L. Goode (40) r> Julie M. Cunningham (41) r> Robert A. Vierkant (42) r> Graham G. Giles (43) (44) r> Laura Baglietto (43) (44) r> Gianluca Severi (43) (44) r> Melissa C. Southey (45) r> Dong Liang (46) r> Xifeng Wu (47) r> Karen Lu (48) r> Michelle A. T. Hildebrandt (47) r> Douglas A. Levine (49) r> Maria Bisogna (49) r> Joellen M. Schildkraut (50) (51) r> Edwin S. Iversen (51) (52) r> Rachel Palmieri Weber (50) r> Andrew Berchuck (53) r> Daniel W. Cramer (54) (55) r> Kathryn L. Terry (54) (55) r> Elizabeth M. Poole (55) (56) r> Shelley S. Tworoger (55) (56) r> Elisa V. Bandera (57) r> Urmila Chandran (57) r> Irene Orlow (58) r> Sara H. Olson (58) r> Elisabeth Wik (59) (60) r> Helga B. Salvesen (60) (61) r> Line Bjorge (60) (61) r> Mari K. Halle (60) (61) r> Anne M. van Altena (62) r> Katja K. H. Aben (63) (64) r> Lambertus A. Kiemeney (63) (65) r> Leon F. A. G. Massuger (62) r> Tanja Pejovic (66) (67) r> Yukie T. Bean (66) (67) r> Cezary Cybulski (68) r> Jacek Gronwald (68) r> Jan Lubinski (68) r> Nicolas Wentzensen (69) r> Louise A. Brinton (69) r> Jolanta Lissowska (70) r> Montserrat Garcia-Closas (71) (72) r> Ed Dicks (73) r> Joe Dennis (74) r> Douglas F. Easton (74) r> Honglin Song (73) r> Jonathan P. Tyrer (73) r> Paul D. P. Pharoah (73) (74) r> Diana Eccles (75) r> Ian G. Campbell (45) (7) (76) r> Alice S. Whittemore (77) r> Valerie McGuire (77) r> Weiva Sieh (77) r> Joseph H. Rothstein (77) r> James M. Flanagan (78) r> James Paul (79) r> Robert Brown (78) r> Catherine M. Phelan (38) r> Harvey A. Risch (80) r> John R. McLaughlin (81) r> Steven A. Narod (82) r> Argyrios Ziogas (83) r> Hoda Anton-Culver (83) r> Aleksandra Gentry-Maharaj (84) r> Usha Menon (84) r> Simon A. Gayther (85) r> Susan J. Ramus (85) r> Anna H. Wu (85) r> Celeste L. Pearce (85) r> Malcolm C. Pike (58) (85) r> Agnieszka Dansonka-Mieszkowska (86) r> Iwona K. Rzepecka (86) r> Lukasz M. Szafron (86) r> Jolanta Kupryjanczyk (86) r> Linda S. Cook (2) (87) (88) r> Nhu D. Le (89) r> Angela Brooks-Wilson (1) (90) r>r>1. Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, V5Z 1L3, Canada r> 2. Department of Population Health Research, Alberta Health Services-Cancer Care, Calgary, AB, Canada r> 3. Departments of Medical Genetics and Oncology, University of Calgary, Calgary, AB, Canada r> 4. Department of Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa, FL, USA r> 5. Department of Medicine, University of British Columbia, Vancouver, BC, Canada r> 6. Genetics and Population Health, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia r> 8. Department of Gynecology and Obstetrics, Comprehensive Cancer Center, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany r> 9. Institute of Human Genetics, Friedrich-Alexander-Universit?t Erlangen-Nürnberg, Erlangen, Germany r> 10. Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA r> 11. Vesalius Research Center, VIB, Louvain, Belgium r> 12. Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Louvain, Belgium r> 13. Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology, Leuven Cancer Institute, Louvain, Belgium r> 14. Section of Biostatistics and Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, NH, USA r> 15. Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA r> 16. Department of Epidemiology, University of Washington, Seattle, WA, USA r> 17. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany r> 18. Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA r> 19. Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA r> 20. Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA r> 21. Department of Obstetrics and Gynaecology, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany r> 22. Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany r> 23. Gynaecology Research Unit, Hannover Medical School, Hannover, Germany r> 24. Aleksandrov Byelorussian Institute for Oncology and Medical Radiology, Minsk, Belarus r> 25. Department of Obstetrics and Gynecology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland r> 26. Department of Pathology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland r> 27. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA r> 28. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA r> 29. Women’s Cancer Research Center, Magee-Womens Research Institute, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA r> 30. The University of Texas School of Public Health, Houston, TX, USA r> 31. Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens Stiftung/Knappschaft GmbH, Essen, Germany r> 32. Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany r> 33. Institut für Humangenetik, Wiesbaden, Germany r> 34. Cedars-Sinai Medical Center, Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA r> 35. Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark r> 36. Department of Gynecology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark r> 37. Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark r> 38. Division of Population Sciences, Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA r> 39. Department of Biostatistics, University of Kansas Medical Center, Kansas, KS, USA r> 40. Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA r> 41. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA r> 42. Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, Rochester, MN, USA r> 43. Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia r> 44. Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Melbourne, VIC, Australia r> 45. Department of Pathology, The University of Melbourne, VIC, Melbourne, Australia r> 46. College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA r> 47. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA r> 48. Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA r> 49. Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA r> 50. Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA r> 51. Cancer Control and Population Sciences, Duke Cancer Institute, Durham, NC, USA r> 52. Department of Statistical Science, Duke University, Durham, NC, USA r> 53. Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA r> 54. Obstetrics and Gynecology Epidemiology Center, Brigham and Women’s Hospital, Boston, MA, USA r> 55. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA r> 56. Channing Division of Network Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA r> 57. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA r> 58. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA r> 59. Department of Pathology, Haukeland University Hospital, Bergen, Norway r> 60. Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway r> 61. Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway r> 62. Department of Gynecology, Radboud University Medical Centre, Nijmegen, Netherlands r> 63. Department for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands r> 64. Comprehensive Cancer Center The Netherlands, Utrecht, The Netherlands r> 65. Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands r> 66. Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA r> 67. Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA r> 68. Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland r> 69. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA r> 70. Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center, Institute of Oncology, Warsaw, Poland r> 71. Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK r> 72. Breakthrough Breast Cancer Research Centre, London, UK r> 73. Department of Oncology, University of Cambridge, Cambridge, UK r> 74. Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK r> 75. Faculty of Medicine, University Hospital Southampton, University of Southampton, Southampton, UK r> 7. Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia r> 76. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia r> 77. Department of Health Research and Policy, Epidemiology, Stanford University School of Medicine, Palo Alto, CA, USA r> 78. Department of Surgery and Cancer, Imperial College London, London, UK r> 79. The Beatson West of Scotland Cancer Centre, Glasgow, UK r> 80. Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA r> 81. Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada r> 82. Women’s College Research Institute, University of Toronto, Toronto, ON, Canada r> 83. Department of Epidemiology, Center for Cancer Genetics Research and Prevention, School of Medicine, University of California-Irvine, Irvine, CA, USA r> 84. Gynaecological Cancer Research Centre, Women’s Cancer, Elizabeth Garrett Anderson Institute for Women’s Health, University College London, London, UK r> 85. Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA r> 86. Department of Pathology, The Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology, Warsaw, Poland r> 87. Division of Epidemiology and Biostatistics, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA r> 88. Department of Community Health Sciences, Faculty of Medicine, University of Calgary, Calgary, AB, Canada r> 89. Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada r> 90. Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada r>
• ISSN：1432-1203

文摘

Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS [56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low-malignant potential (LMP) serous, and 24 for invasive serous EOC], selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95?% confidence intervals are reported. Nine variants tagging six loci were associated with subtype-specific EOC risk at P?<?0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR?=?1.17, P?=?0.029, n?=?1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P?=?0.014, n?=?2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR?=?0.86, P?=?0.0043, n?=?892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR?=?0.84, P?=?0.0007) and LMP serous EOC risk remained statistically significant at P?<?0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes.